anti biotics

Antibiotics are drugs derived wholly or partially from certain microorganisms and are used to treat bacterial or fungal infections.

Antibiotics either kill microorganisms (bactericidal) or stop them from reproducing (bacteriostatic).

Antibiotics are among the most frequently prescribed medications in modern medicine.

Today, over 100 different antibiotics are available to doctors to cure minor discomforts as well as life-threatening infections.

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Up to 80% of antibiotics are prescribed in the outpatient setting:› URTI's› UTI's

50% of office visits colds and upper RTI’s

80% of visits for acute bronchitis…are treated with antibiotics.

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B-LACTAMS.

Aminoglycosides.

Quinolones.

Sulphonamides.

Macrolides.4

1.Inhibit synthesis of bacterial cell wall.

2.Act directly on the cell membrane of the bacteria, causing it to break open.

3.Inhibit bacterial protein synthesis.(nucleic acid synthesis , interferes with ribosomal

functions)

4.Affect bacterial metabolism and growth.5

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Their biological source:› Plant, mold, soil microorganisms

Their spectrum of action or coverage:› Broad/wide spectrum - effective against a wide

range of bacteria › Narrow spectrum - effective mainly against

specific categories of bacteria e.g. Gram-positive or Gram-negative bacteria

but not both› Limited spectrum - effective against a single

organism or disease Their mode of action:

› How they fight bacteria7

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Specific agents› Penicillin G (IV), Penicillin V (oral)› Antistaphylococcal

nafcillin, oxacillin, dicloxacillin› Extended spectrum

ampicillin, amoxicillin ticarcillin, piperacillin

Clinical uses› Streptococcal phayngitis (PCN)› MSSA (nafcillin)› E.coli, Proteus (ampicilin)› Pseudomonas (piperacillin)

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Mechanism of action› Inhibits bacterial cell wall synthesis› Bind to Penicillin binding proteins› Bactericidal

Mechanisms of resistance› Altered penicillin binding proteins (PBPs)

mecA/MRSA, Strep. Pneumo resistance

› Production of Beta-lactamases (penicillinases)

› Decreased penetration/increased efflux (pseudomonas)

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Enzymes produced by bacteria which destroy beta-lactam antibiotics

Many different types› Penicillinases, cephalosporinases,

carbapenemases Narrow spectrum vs. extended

spectrum Most are plasmid mediated

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Clavulanate› With amoxicillin (Augmentin)› With ticarcillin (Timentin)

Sulbactam› With ampicillin (Unasyn)

Tazobactam› With piperacillin (Zosyn)

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Adverse effects› Allergy (Anaphylaxis, rash, fever,

interstitial nephritis)› Diarrhea –amoxicillin/clavulanate

(augmentin)› Rash - ampicillin› Sodium overload- ticarcillin› Seizure especially with high doses and

renal dysfunction

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1st generation – cefazolin 2nd generation - cefuroxime 3rd generation - ceftriaxone 4th generation - cefepime 5th generation - ceftobiprole Differ in spectrum, resistance to

beta lactamases, penetration into CNS

IV, IM: oral forms for 1st, 2nd,3rd gen.

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Clinical uses› Cellulitis – (cephalexin)› Prophylactic prior to surgery

(cefotetan)› Meningitis – (ceftriaxone)

Mechanism of action› Inhibition of cell wall synthesis› Bactericidal

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Resistance mechanisms› Destruction by beta-lactamases

(cephalosporinases)› Alteration in the affinity of penicillin

binding proteins (PBPs) for cephalosporins

› Efflux of cephalosporins from microbe

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Adverse Effects Allergic reactions – 10% cross

reactivity with penicillins GIT disturbances. Pain & inflammation at site of

injection. Bleeding disorders and disulfiram-

like effect.

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Specific agents› Imipenem

With cilastin (Primaxin)

› Meropenem (Merrem)

› Ertapenem (Invanz)› Doripenem (Doribax)› IV only› Broad spectrum

Gram positives Gram negatives Pseudomonas

(except ertapenem

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Clinical uses› Intraabdominal infections› Polymicrobial infections› Pseudomonas aeruginosa› Neutropenic fever

Mechanism of action› Inhibit bacterial cell wall synthesis› Bactericidal

Adverse effects› Nausea/vomiting› Allergy – Significant cross reaction with pencillin

allergy› Seizure

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Aztreonam (Azactam) IV only Antimicrobial spectrum

› Gram negative aerobic bacteria only

› Including Pseudomonas Inhibits cell wall

synthesis Bactericidal Adverse effects

› Allergy (<1% cross-reactive with penicillin)

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Specific agents› Gentamicin› Tobramycin› Amikacin

IV/IM/inhaled Spectrum of action

› Aerobic Gram negative bacteria

› Pseudomonas spp., E.coli, others

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Mechanism of action› Inhibit bacterial protein synthesis› Bactericidal

Mechanisms of resistance› Bacterial production of enzyme that

inactivates aminoglycosides› Alteration of drug target site› Altered drug transport

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Adverse effects› Nephrotoxicity› Ototoxicity› Vestibular toxicity› Neuromuscular (myasthenia gravis)

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Specific agents› Norfloxacin› Ciprofloxacin› Levofloxacin

(Levaquin)› Gatifloxacin (Tequin)› Moxifloxacin

(Avelox)› Nalidixic acid

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Spectrum of actionBroad spectrum (varies by

agent) Inhibit DNA synthesis Bactericidal Mechanisms of resistance

› Change in target enzyme› Change in permeability of organism

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Adverse Effects› Nausea/vomiting› CNS – headache, confusion (in elderly),

panic attack, anxiety, nightmares› Tendonitis or tendon rupture› Kidney stones due to loss of Oxalobacter

formigenes.› Drug-Drug interactions with NSAID,

Theophylline.

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Spectrum of activity› Gram positives and some gram negatives

Beta-hemolytic streptococci, staphylococci and enterococci Some pneumococcal

› Mycoplasma and legionella› Chlamydia

Specific agents› Erythromycin› Azithromycin (Unizithrin)› Clarithromycin (Klacid)

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Mechanism of action› Inhibit bacterial protein synthesis› Bacteriostatic in small concentration &

Bactericidal in high concentration Mechanism of resistance

› Decreased permeability of drug into the microbe

› Modification of target sites› Hydrolysis of macrolide by bacterial enzymes

Adverse effects› Gastrointestinal› Arrhythmias› Liver toxicity

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Antimicrobial spectrum› Anaerobes› Some gram positives

Inhibits bacterial protein synthesis

Bacteriostatic Adverse effects

› Nausea, diarrhea› Clostridium difficile

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Clinical use› Broad spectrum› Also Mycoplasma

pneumonia, Chlamydia, Rickettsia, Lyme disease

Specific agents› Tetracycline› Doxycycline

(Vibramycin)› Minocycline (Minocin)

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Inhibit bacterial protein synthesis Bacteriostatic

Adverse effects› Food drug interaction (food and dairy interfere with

absorption)› Also occurs with some antacids› GI irritation› Hepatic toxicity› Renal toxicity› Photosensitivity› Discoloration of teeth › Vertigo (Minocycline)

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Specific agents› Sulfisoxazole› Sulfamethoxazole/

trimethoprim (Bactrim)› Trimethoprim

Clinical uses› Broad spectrum (gram +

and gram -)› Oral – UTIs› Topical – burn wounds,

opthalmic preps› Pneumocystis, Nocardia

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Mechanism of action› Inhibit folic acid synthesis› Bacteriostatic

Mechanism of resistance› Alternate mechanisms for folate synthesis› Sulfa not usually used alone due to resistance

Adverse Effects› Hypersensitivity› Hematologic toxicity› Renal toxicity› CNS› Photosensitivity› Hematopoetic › Drug interactions

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Mechanism of action› Inhibits bacterial cell

wall synthesis Bactericidal? Spectrum

› Gram positive bacteria

› Methicillin resistant Staphylococcus aureus

› Clostridium difficile (oral)

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Mechanisms of resistance› Production of a new

cell wall component that vancomycin doesn’t inhibit

Adverse Effects› Red Man’s

syndrome› Rash› Renal toxicity› Ototoxicity› Leukopenia

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Linezolid (Zyvox)

Mechanism of action› Inhibit bacterial protein

synthesis

Bacteriostatic or bactericidal

IV/oral

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Antimicrobial spectrum› Anaerobes

(Clostridium difficile, Bacteroides)

› Protozoa (Trichomonas, Entamoeba histolytica)

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Mechanism of action› Not completely understood› Metronidazole is a prodrug› Metabolism of the drug produces toxic

metabolites› Bactericidal

Adverse effects› Metallic taste› Peripheral neuropathy› Disulfuram effect – interaction with

ethanol

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Microbiological activity.

Concentration at site of infection.

How long it will remain at the site of action.

MIC.

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Using AB only when absolutely needed and indicated:

AB often abused for viral infections (diarrhea, flu-symptoms, etc.)

– Starting with narrow-spectrum drugs – Limiting use of newer drugs – Identifying the infecting organism – Defining the drug sensitivity of the infecting

organism – Considering all host factors:site of infection, inability of drug of choice to penetrate

the site of infection, etc. – Using AB combinations only when indicated:Severe or mixed infections, prevention of resistance

(tuberculosis) Worldwide more than 500 metric tons antibiotics are

used anually !!!48